自然衰老过程中小鼠海马神经发生的改变  

Changes of mouse hippocampal neurogenesis during aging

作　　者：刘品月 晋贞超 邓小兰[1] 袁莉[1] 郑敏[1] 王亚平[1] 王健[2] 姜蓉[1] 

机构地区：[1]重庆医科大学干细胞与组织工程研究所,重庆市400016 [2]重庆医科大学附属第二医院神经内科,重庆市400016

出　　处：《中国组织工程研究》2016年第11期1564-1569,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(31100985);重庆市自然科学基金(CSTC2010BB5096)~~

摘　　要：背景:多篇文献报道在衰老期海马神经发生出现障碍,最终导致学习记忆能力的减退。但是究竟哪个环节的改变导致这种减退的发生并不明确。目的:了解衰老过程中小鼠海马齿状回颗粒下层神经发生的改变。方法:选取3个年龄组的小鼠,免疫组织化学法观察海马齿状回颗粒下层神经干细胞(nestin+)、成神经+细胞(Doublecortin,DCX+)和增殖细胞(PCNA+)的个数;反转录PCR观察海马衰老相关基因p19Arf、p21Cip1/Waf1 mR NA的表达。结果与结论:老年组与青年组和中老年组相比PCNA+细胞、nestin+细胞与DCX+细胞数量明显减少;p19Arf、p21Cip1/Waf1mR NA表达明显增强。结果说明,衰老小鼠海马齿状回颗粒下层细胞增殖减少,神经干细胞数量减少,向神经元方向分化减少,颗粒下层区神经发生下降可能与增殖相关基因表达增加相关。提示自然衰老过程中海马组织神经发生的下降可能与p19Arf-Mdm2-p53-p21Cip1/Waf1信号通路中p19Arf、p21Cip1/Waf1的表达上调有关。BACKGROUND： Abnormal hippocampal neurogenesis during aging has been reported to result in learning and memory dysfunction. But its mechanism is unclear.OBJECTIVE： To understand the changes of mouse neurogenesis in the hippocampal subgranular zone during aging. METHODS： C57BL/6 mice 2, 6 and 20 months of age were used. Immunochemistry was used to count the number of neural stem cells（nestin＋）, neuroblasts（Doublecortin＋, DCX＋）, and proliferative cells（proliferating cell nuclear antigen＋, PCNA＋） in the hippocampal subgranular zone. m RNA expressions of aging-related genes, p19 Arf and p21Cip1/Waf1, in the hippocampus were detected by reverse transcription-PCR. RESULTS AND CONCLUSION： Compared with the young and middle age groups, the number of PCNA＋ cells, nestin＋ and DCX＋ cells in the hippocampal subgranular zone of the aged group decreased dramatically; the expression of p19 Arf and p21Cip1/Waf1 m RNA increased in the aged group. Proliferation activity, the number of neural stem cells and neuronal differentiation all decreased. These findings indicate that the decline of hippocampal neurogenesis may be associated with increased expression of aging-related genes p19 Arf and p21Cip1/Waf1 in the p19Arf-Mdm2-p53-p21Cip1/Waf1 pathway.

关 键 词：衰老 海马 神经干细胞 组织构建 组织工程 衰老 海马 神经发生 颗粒下层 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]